ALL Backbone in AYAs

Official title

Treatment of Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYAs)

Overview

The goal of this research study is to evaluate a chemotherapy regiment for the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs). The names of the study drugs involved in this study are: * blinatumomab (a type of immunotherapy drug) * cyclophosphamide (a type of chemotherapy drug) * cytarabine (a type of antineoplastic agent) * dexamethasone (a type of synthetic glucocorticoid) * doxorubicin (a type of antineoplastic agent) * etoposide (a type of antineoplastic agent) * mercaptopurine (a type of antineoplastic agent) * methotrexate (a type of chemotherapy drug) * pegaspargase (a type of antineoplastic agent) * vincristine (a type of antineoplastic agent)

Detailed description

This Phase 2, single-arm research study is to evaluate a chemotherapy regiment the treatment of newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs).

The U.S. Food and Drug Administration (FDA) has approved all of the drugs of treatment being studied but the investigators of this research study want to understand more about the safety and effectiveness of the chemotherapy regimen in adolescents and young adults with newly diagnosed Philadelphia chromosome-negative ALL.

The research study procedures include screening for eligibility, in-clinic visits, blood tests, urine tests, saliva tests, X-rays, electrocardiograms (ECGs), echocardiograms (ECHOs), Dual-Energy X-ray Absorptiometry (DEXA) scans, bone marrow aspirations/biopsies.

Participation in this study is expected to last about 10 years, 2 years of treatment followed by 8 years of follow up.

It is expected that about 67 people will take part in this research study.

Interventions

• Drug Blinatumomab
  A bispecific T-cell engager (BiTE) antibody, single-use vial via intravenous infusion, per standard of care
• Drug Oncaspar
  A modified enzyme L-asparaginase, single-use vial via intravenous infusion, per standard of care
• Drug Cyclophosphamide
  An alkylating agent, single-use vial via intravenous infusion, per standard of care
• Drug Cytarabine
  An antineoplastic antimetabolite, multi-dose vial via intrathecal injection (through the spinal space), per standard of care
• Drug Dexamethasone
  A synthetic glucocorticoid, tablets or single-use vials via orally or intravenous infusion (through the vein), per standard of care
• Drug Doxorubicin Hydrochloride
  An anthracycline antibiotic, single-use or multi-dose vials via intravenous infusion, per standard of care
• Drug Etoposide
  A derivative of podophyllotoxin, multi-dose vial via intravenous infusion, per standard of care
• Drug Mercaptopurine
  A purine antagonist, tablet via orally, per standard of care
• Drug Methotrexate
  A folate analogue, multi-dose and single-use vials via intrathecal injection, per standard of care
• Drug Vincristine
  A vinca alkaloid, single-use vials via intravenous injection, per standard of care

Primary outcome measures

• Treatment Completion Rate Through Time Point 3 (TP3) [Time frame: Timeframe for TP3 depends on disease immunophenotype. Participants with CD19-positive B-ALL, TP3 occurs at the end of Blinatumomab Cycle 2 on Day 28 (130 days from study start). For participants with T-cell ALL or those who do not receive blinatum]

Secondary outcome measures (12)

• Rate of Treatment-Related Mortality (TRM) [Time frame: Up to 115 weeks]
• Rate of Treatment Discontinuation due to Toxicity or Disease [Time frame: Up to 115 weeks]
• Rate of Asparaginase Non-Completion [Time frame: This endpoint is assessed during Consolidation II, which occurs approximately from Day 270 to Day 480 of study treatment.]
• Reason of Asparaginase Non-Completion [Time frame: Up to 115 weeks]
• Grade 3 Infections Toxicity Rate [Time frame: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks.]
• Grade 3 Asparaginase-associated Toxicities Rate [Time frame: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks.]
• Grade 3 Orthopedic Toxicity Rate [Time frame: Adverse events will be followed for 30 days after completion of protocol treatment, with the overall treatment period up to 115 weeks. Ostenonecrosis and fractures will be followed up to 10 years.]
• Complete remission Rate (CRR) [Time frame: CR can be documented either at the end of Induction IA (32 days) or Induction IB (74 days).]
• Measurable Residual Disease (MRD) Negativity Rate at the end of Induction IA (Time Point 1) [Time frame: At the end of Induction IA (32 days from study start)]
• Measurable Residual Disease (MRD) Negativity Rate at the end of Induction IB (Time Point 2) [Time frame: At the end of Induction IB (74 days from study start)]
• Measurable Residual Disease (MRD) Negativity Rate at Time Point 3 (TP3) [Time frame: For CD19-positive B-ALL, TP3 is reached at the end of Blinatumomab Cycle 2 on Day 28 (Day 130 from study start). For T-cell ALL or participants not receiving blinatumomab, TP3 occurs on Day 28 of Consolidation IC (Day 102 from study start).]
• Median Event-Free Survival (EFS) [Time frame: Up to 10 years]

Eligibility criteria

Inclusion criteria

3.1.1Confirmed diagnosis of Philadelphia chromosome-negative acute lymphoblastic leukemia.

• Diagnosis should be made by peripheral blood, bone marrow aspirate, bone marrow biopsy, or tissue biopsy demonstrating ≥25% involvement by lymphoblasts, with flow cytometry or immunohistochemistry confirming B-ALL or T-ALL.

o Participants with B-cell and T-cell lymphoblastic lymphoma are eligible regardless of bone marrow involvement Participants with mixed phenotype acute leukemia (MPAL) ARE eligible, if an ALL regimen is felt to be most appropriate treatment.

• Participants with CNS leukemia ARE eligible. 3.1.2 Allowed prior therapy:
• Corticosteroids, hydroxyurea, all-trans retinoic acid (ATRA).
• IT chemotherapy.
• Emergent radiation therapy or leukapheresis for life threatening complications.
• One cycle of prior chemotherapy (i.e. an induction cycle given at another institution and participant transfers care for post-induction treatment; OR a participant does not meet eligibility prior to induction but does meet eligibility after remission induction).

3.1.3 Age 18.00 - 50.99 years 3.1.4 Direct bilirubin <1.4 mg/dL (total bilirubin < 1.4 mg/dL is acceptable). 3.1.5 Willingness to use effective means of birth control. The effects of chemotherapy on the developing human fetus are unknown. For this reason and because therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study.

3.1.6 Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

Philadelphia chromosome-positive / BCR::ABL1 fusion 3.2.2 Participants with mature B-cell (Burkitt's) ALL. Mature B-cell ALL is defined by the presence of surface immunoglobulin AND any of the following: t(8;14)(q24;q32), t(8;22), t(2;8), or c-myc-gene rearrangement by FISH, PCR or other testing. \[FISH/PCR testing for c-myc rearrangements is not required prior to study entry, but it is suggested for participants with surface immunoglobulin expression or L3 morphology\]. 3.2.3 Participants with acute undifferentiated leukemia. 3.2.4 Participants receiving any other investigational agent for this condition.

3.2.5 Uncontrolled intercurrent illness including but not limited to ongoing infection with vital sign instability (hypotension, respiratory insufficiency), life-threatening acute tumor lysis syndrome (e.g., with renal failure), symptomatic congestive heart failure, cardiac arrhythmia, intracranial or other uncontrolled bleeding. Circumstances that may significantly interfere with a participant's ability to safely comply with study procedures, such as attend scheduled study visits, adhere to treatment protocols, or complete study assessments. These include a lack of reliable transportation, unstable housing, or psychiatric illness, but reasonable attempts should be made to overcome these circumstances, including but not limited to identifying sponsor, institutional, or thirdparty financial or social support as well as psychiatric consultation for objective assessment. 3.2.6 Sexually active participants of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation are ineligible.

3.2.7 Pregnant women are excluded from this study because many of the agents used on this protocol have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these chemotherapy agents, breastfeeding should be discontinued if the mother is enrolled.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07227584 · 25-533

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗